The granulocyte macrophage colony stimulating factor (GM-CSF) regulates amyloid beta (Abeta) production

Cytokine
Claude-Henry VolmarM Mullan

Abstract

One of the hallmarks of Alzheimer's disease (AD) is the accumulation of amyloid beta (Abeta) plaques in the brain parenchyma. An inflammatory component to AD has been suggested in association with increased cytokine release. We have previously shown that CD40L stimulation of microglia induces increases in pro-inflammatory cytokines such as interleukin-1beta (IL-1beta), IL-6, IL-8 and GM-CSF. We have also shown that CD40L stimulation increases Abeta levels in HEK-293 cells over-expressing both the amyloid precursor protein (APP) and CD40 (HEK/APPsw/CD40). In this study, we show that GM-CSF neutralizing antibodies mitigate the CD40L-induced production of Abeta in HEK/APPsw/CD40 cells. In addition, we demonstrate that treatment of these cells with recombinant GM-CSF significantly increases Abeta levels. Furthermore, we show that shRNA silencing of the GM-CSF receptor gene significantly reduces Abeta levels to below base line in non-stimulated HEK/APPsw/CD40 cells. Analysis of cell surface proteins revealed that silencing of the GM-CSF receptor also decreases APP endocytosis (therefore reducing the availability of APP to be cleaved in the endosomes). Taken together, our results suggest that GM-CSF operates downstream of CD40/CD40L ...Continue Reading

References

Jun 15, 1990·Biochemical and Biophysical Research Communications·K OhnoT Marunouchi
Mar 10, 2001·Acta Neurologica Scandinavica·E TarkowskiA Tarkowski
Jun 30, 2004·Brain Research·J Todd RoachMichael Mullan
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Jan 16, 2007·Nature Genetics·Ekaterina RogaevaPeter St George-Hyslop
Apr 17, 2007·The European Journal of Neuroscience·Ghania Ait-GhezalaMichael Mullan
Aug 19, 2007·European Journal of Immunology·Marcela RosasPhilip R Taylor

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Citations

Jul 31, 2013·Journal of Molecular Cell Biology·Gaëlle Naert, Serge Rivest
Jun 15, 2010·Muscle & Nerve·Ryan M MitchellJames R Connor
Sep 21, 2011·Cytokine·A X S SantosF C R Guma
Apr 22, 2017·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Hu ZhangDeshu Shang
Jul 19, 2018·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Pei-Pei Guan, Pu Wang
Nov 7, 2018·Proceedings of the National Academy of Sciences of the United States of America·Karolina J JanczuraClaes Wahlestedt

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